T helper cell subtypes Th1 and Th2 originate from common naïve precursor cells (Thp) in response to antigen and cytokine stimulation. Although, Th cells have a crucial role in host defence against intracellular and extracellular pathogens, disturbances in the balance between Th1 and Th2 responses can promote or lead to pathogenesis of immune-mediated diseases. Enhanced Th2 responses are involved in atopic diseases, such as asthma, whereas dominating Th1 responses are implicated in certain autoimmune diseases, such as type 1 diabetes or rheumatoid arthritis (1). For understanding the molecular mechanisms driving the pathogenesis of these diseases, it is essential to elucidate the early differentiation process of Th1 and Th2 cells in detail.
Some of the central factors involved in directing the differentiation process have been identified. IL12/STAT4 and IFNγ/STAT1 signaling are important in driving Th1 polarization, whereas IL4/STAT6 signaling directs Th2 polarization (2). Transcription factors TBX21 and GATA3 are also among the key factors required for the Th1 and Th2 differentiation, respectively (3-6). Although many players implicated in the regulation of differentiation have been recognized, the current model as such is still too simple to explain the process in detail and also other factors must be involved.
Recently, increasing number of studies has utilized DNA microarrays to identify new factors involved in the Th1 and Th2 polarization in human and mouse (7-14). However, all of these studies have focused on studying limited number of primarily known genes. In our recent studies we have elucidated regulation of approximately 9300 genes with primarily known function during the early differentiation of human Th1 and Th2 cells (10), (unpublished data). In this study we have extended the previous work by exploring the regulation of the rest of genes in the human genome. Based on current and our previous studies altogether 297 genes, representing approximately 1% of the human genome, are involved in the early Th1 and Th2 cell polarization during the first two days.